Perspective: IL-15 cytokine-armored NK cells as ready-to-use immunotherapy for diverse malignancies: therapeutic potential and toxicity risks
Year: 2025
Type: article
Abstract: Natural killer (NK) cells have been engineered to express chimeric antigen receptors (CARs) to enhance their cytotoxic capabilities through CAR-mediated activation, a strategy that has yielded promising advancements in cancer treatment in recent pre-clinical and clinical trials. However, the use of CAR-NK cells for the treatment of solid tumors has presented challenges due to limited in vivo CAR-NK efficacy, expansion, persistence, and the suppressive tumor microenvironment. Many groups have developed IL-15 cytokine-armored CAR-NK therapeutics targeting various cancers to overcome these challenges. However, preclinical in vivo studies using immunodeficient mice have encountered instances of significant toxicity without evidence of cytokine release syndrome. The lack of an intact immune system likely allows for unchecked in vivo expansion of cytokine armored CAR-NK cells, leading to early mortality in immunodeficient mice following treatment with these cells. We speculate that the use of humanized mice will allow for engraftment of tumor and alleviate cytokine armored CAR-NK toxicity, thereby allowing for effective assessment of CAR-NK efficacy in the absence of toxicity.
Source: Frontiers in Immunology
Institutions: University of Minnesota, Masonic Cancer Center
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Awards: G1005149074, G1345980661, G1442899210, G4690314899, G6159438681, G6433449787, Pediatric Ohio-New York Cancer (Peds-ONC) Immunotherapy Center, Engineered B Cells as a Universal Platform for the Treatment of Enzymopathies, G9000167443, Integrated Immune Engineering for Poor Prognosis Cancers, Center for Multiparametric Imaging of Tumor Immune Microenvironments, Cancer Center Support Grant
OpenAlex ID: W4416402622